The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index; none of the 31 sources its claims cite is checked for support yet.
Adult-onset pulmonary fibrosis caused by mutations in telomerase
Open accessAbstract
Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology. Some individuals with IPF have a familial disorder that segregates as a dominant trait with incomplete penetrance. Here we used linkage to map the disease gene in two families to chromosome 5. Sequencing a candidate gene within the interval, TERT , revealed a missense mutation and a frameshift mutation that cosegregated with pulmonary disease in the two families. TERT encodes telomerase reverse transcriptase, which together with the RNA component of telomerase ( TERC ), is required to maintain telomere integrity. Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT . A heterozygous mutation in TERC also was found in one family. Heterozygous carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family members without the mutations. Thus, mutations in TERT or TERC that result in telomere shortening over time confer a dramatic increase in susceptibility to adult-onset IPF.
Overview
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Written from the paper’s full text.
TL;DR
Mutations in *TERT* or *TERC* that cause telomere shortening confer susceptibility to adult-onset idiopathic pulmonary fibrosis (IPF). The study links telomerase dysfunction to familial and sporadic IPF, with incomplete penetrance and possible smoking exacerbation.
Key findings
- Linkage in two large families mapped disease to chromosome 5p15 with a maximal LOD score of 2.8; sequencing the candidate gene *TERT* found a missense mutation (R865H) and a frameshift mutation (V747fsX766) that cosegregated with pulmonary disease.
- In 44 additional unrelated familial interstitial lung disease probands and 44 sporadic cases, five other *TERT* mutations were found (total: two frameshift deletions and five missense mutations), plus one heterozygous *TERC* mutation (r.37a>g); none of the seven *TERT* mutations were found in 94 ethnically matched controls, 200 patients with aplastic anemia, or a multiethnic panel of 528 controls.
- Heterozygous carriers of *TERT* or *TERC* mutations had shorter telomeres than age-matched family members without the mutations; in vitro TRAP assays showed frameshift mutants had little detectable telomerase activity, missense and *TERC* mutants ranged from zero to 100% of wild-type activity, and mixing V747fs with wild-type *TERT* suggested haploinsufficiency.
- Among mutation carriers, smokers died at an average age of 58 years (n = 13) versus 68 years for nonsmokers (n = 7); all affected individuals developed pulmonary fibrosis in adulthood with no history of pediatric lung disease.
Methods
- Clinical sample: 46 families with two or more cases of idiopathic interstitial lung disease (34 of 46 families had individuals with IPF) and 44 sporadic interstitial lung disease cases (31 with IPF); genomic DNA was isolated from leukocytes, and for four individuals from formalin-fixed paraffin-embedded archival samples.
- Linkage analysis: whole-genome SNP genotyping with the Illumina Linkage IVb panel of >6,000 polymorphic SNPs; MERLIN was used for multipoint model-free and model-based linkage analysis, with the highest peak on chromosome 5p15.
- Mutation and functional analysis: *TERT* exons and splice sites and 451 bp encoding *TERC* were sequenced; telomerase activity was measured by the TRAP assay using in vitro coexpressed recombinant protein and RNA; telomere length was assessed by terminal restriction fragment (TRF) Southern blot analysis of leukocyte DNA.
Limitations
- The paper does not include a formal limitations section; it states that pulmonary fibrosis appears to be a human-specific manifestation of telomerase deficiency and that it is not yet reported whether aged telomerase-deficient mice develop similar lung pathology.
- The paper notes incomplete penetrance: some family members who inherited a *TERT* mutation had no evidence of pulmonary disease, and environmental influences such as cigarette smoking may affect the phenotype.
- Evident from the text: linkage mapping relied on two families, mutation screening focused on the candidate genes *TERT* and *TERC*, and in vitro TRAP activity did not always track telomere shortening because some mutations caused telomere shortening without a detectable decrease in telomerase activity.
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24 Own result · 21 Not checked yet · 8 Own interpretation · 4 Own method · 1 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sequencing a candidate gene within the interval, TERT, revealed a missense mutation and a frameshift mutation that cosegregated with pulmonary disease in the two families.”
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In the paper
“A heterozygous mutation in TERC also was found in one family.”
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In the paper
“Here we used linkage to map the disease gene in two families to chromosome 5.”
- Also stated in: § Results · plain
“Both families displayed linkage to chromosome 5p15 with a maximal logarithm of odds (LOD) score of 2.8.”
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT.”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“Heterozygous carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family members without the mutations.”
- Also stated in: § Results · plain
“When compared with normal family members of similar age, the mean telomere length was significantly shorter for those individuals who were heterozygous for a mutation in TERT or TERC (Fig. 5 A and B).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, a total of two frameshift deletions and five missense mutations in TERT were identified in patients with pulmonary fibrosis (Fig. 3).”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“When telomere lengths were analyzed within families, the family members with clinical disease tended to have shorter TRFs than the asymptomatic carriers.”
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In the paper
“Mixing different amounts of the V747fs TERT construct with the wild-type TERT construct did not affect the activity of the wild-type protein, suggesting a mechanism of haploinsufficiency (Fig. 4D).”
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In the paper
“The proband of family F11 was heterozygous for a transition mutation (CGT → CAT) in codon 865 that is predicted to change a highly conserved arginine to a histidine.”
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In the paper
“The five missense mutations in TERT (Fig. 4 B and C) and the mutation in TERC (Fig. 4 A and C) produced levels of telomerase activity that ranged from zero to 100% of wild-type activity.”
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“Four additional sequence variations, including three missense mutations and one 177-bp deletion, were found (Fig. 3).”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“None of the seven mutations were found in 94 locally collected, ethnically matched individuals, nor were they detected in 200 patients with aplastic anemia or a multiethnic panel of 528 individuals sequenced as controls (9).”
What the sources say
- Not checked yetcites [9] Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. N Engl J Med. 2005;352:1413–1424. doi: 10.1056/NEJMoa042980. [DOI] [PubMed] [Google Scholar] source
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In the paper
“All developed pulmonary fibrosis during their adult years with no history of pediatric lung disease, in contrast with kindreds associated with surfactant protein C mutations (18, 19).”
What the sources say
- Not checked yetcites [18] Thomas AQ, Lane K, Phillips J, III, Prince M, Markin C, Speer M, Schwartz DA, Gaddipati R, Marney A, Johnson J, et al. Am J Respir Crit Care Med. 2002;165:1322–1328. doi: 10.1164/rccm.200112-123OC. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [19] Nogee LM, Dunbar AE, III, Wert SE, Askin F, Hamvas A, Whitsett JA. N Engl J Med. 2001;344:573–579. doi: 10.1056/NEJM200102223440805. [DOI] [PubMed] [Google Scholar] source
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In the paper
“None had aplastic anemia but several exhibited a mild to moderate anemia and one individual developed neutropenia after lung transplantation.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“One additional missense mutation was identified involving the same arginine at codon 865 found to be mutated in family F11.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Another individual with a TERT mutation in this family had very short TRFs but did not have IPF. This individual had cirrhosis of unknown etiology.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The proband of family F31 was heterozygous for a deletion of thymidine at position 2240 in the cDNA, which creates a frameshift in the reading frame and is predicted to result in a truncated protein missing half of the reverse-transcriptase domain and the entire C-terminal region.”
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In the paper
“As expected, the mutation (V747fs, Fig. 4 A and C) missing half the reverse transcriptase domain and the mutation (E1116fs; Fig. 4C) missing the C-terminal E-IV domain had very little detectable telomerase activity.”
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In the paper
“This change was not detected in 94 ethnically matched controls but was identified previously in a person with severe aplastic anemia who was a compound heterozygote for variants in TERC (12).”
What the sources say
- Not checked yetcites [12] Ly H, Schertzer M, Jastaniah W, Davis J, Yong SL, Ouyang Q, Blackburn EH, Parslow TG, Lansdorp PM. Blood. 2005;106:1246–1252. doi: 10.1182/blood-2005-01-0247. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper
“A number of individuals had evidence of axial osteoporosis; in many cases, this diagnosis preceded or was determined in the absence of lung disease.”
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In the paper
“For both families, some family members with TERT mutations exhibited other clinical features of DKC (7), such as osteoporosis/osteopenia, anemia and cancer (Table 1), but none of the affected individuals had the mucocutaneous lesions typical of DKC.”
What the sources say
- Not checked yetcites [7] Dokal I. Br J Haematol. 2000;110:768–779. doi: 10.1046/j.1365-2141.2000.02109.x. [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The individuals with TERT or TERC mutations have none of the physical manifestations of DKC and were all ascertained by the lung fibrosis phenotype, distinguishing them from previously described patients with mutations in these genes (6, 9, 10, 17).”
What the sources say
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [9] Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. N Engl J Med. 2005;352:1413–1424. doi: 10.1056/NEJMoa042980. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [10] Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I. Nature. 2001;413:432–435. doi: 10.1038/35096585. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [17] Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM, Sloand E, Zeng WS, Read EJ, Lansdorp PM, Young NS. Lancet. 2003;362:1628–1630. doi: 10.1016/S0140-6736(03)14797-6. [DOI] [PubMed] [Google Scholar] source
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In the paper
“One proband of a Caucasian family (F61) was heterozygous for an adenosine and guanine at position 37.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology.”
- Also stated in: § Abstract · plain
“IPF is distinguished from the other interstitial lung diseases by its unknown etiology, by characteristic abnormalities on pulmonary function tests and radiographs, and by biopsy findings, which include evidence of injury occurring over time with foci of replicating fibroblasts at the interface between normal and scarred lung tissue (3).”
What the sources say
- Not checked yetcites [3] American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med. 2002;165:277–304. doi: 10.1164/ajrccm.165.2.ats01. [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Among the genes we evaluated was TERT, which was considered a candidate because a mutation in this gene was recently reported to cause autosomal dominant dyskeratosis congenita (DKC), a disorder in which 20% of affected individuals develop pulmonary fibrosis (6, 7).”
What the sources say
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [7] Dokal I. Br J Haematol. 2000;110:768–779. doi: 10.1046/j.1365-2141.2000.02109.x. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The clinical presentation of familial IPF is indistinguishable from sporadic IPF except that the age of onset tends to be earlier (55 years vs. 67 years) (4, 5).”
What the sources say
- Not checked yetcites [4] Marshall RP, Puddicombe A, Cookson WO, Laurent GJ. Thorax. 2000;55:143–146. doi: 10.1136/thorax.55.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [5] Johnston ID, Prescott RJ, Chalmers JC, Rudd RM. Thorax. 1997;52:38–44. doi: 10.1136/thx.52.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper
“All sequences were determined in both directions, the mutations were confirmed by three separate PCR amplification products, and both genes were sequenced in their entirety for all subjects.”
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In the paper
“Telomere length is also influenced by oxidative damage (24) that, in part, may explain why lung disease is the predominant phenotype and why smoking may exacerbate this disease.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The pathologic features of IPF suggest that the lung injury is focal, affecting scattered portions of the lung parenchyma and recurring over many years (21).”
What the sources say
- Not checked yetcites [21] Katzenstein AL, Myers JL. Am J Respir Crit Care Med. 1998;157:1301–1315. doi: 10.1164/ajrccm.157.4.9707039. [DOI] [PubMed] [Google Scholar] source
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In the paper
“Repeat experiments showed the same relative trend of TRAP activities.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Multiple different mutations in TERC have been described for patients with DKC (10).”
What the sources say
- Not checked yetcites [10] Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I. Nature. 2001;413:432–435. doi: 10.1038/35096585. [DOI] [PubMed] [Google Scholar] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pulmonary fibrosis appears to be a human-specific manifestation of telomerase deficiency.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Call rates varied from 99.7–100% for Autopure-purified DNA and between 72–98% for whole-genome-amplified DNA extracted from archival samples.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Telomerase may be a marker for identifying resident stem cells that promote regeneration and prevent premature aging of the lung.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Smoking causes telomere shortening in a dose-dependent manner (22) and is associated with familial interstitial pneumonia (23).”
What the sources say
- Not checked yetcites [22] Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG. Eur Respir J. 2006;27:525–528. doi: 10.1183/09031936.06.00087005. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [23] Steele MP, Speer MC, Loyd JE, Brown KK, Herron A, Slifer SH, Burch LH, Wahidi MM, Phillips JA, III, Sporn TA, et al. Am J Respir Crit Care Med. 2005;172:1146–1152. doi: 10.1164/rccm.200408-1104OC. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, a recent trial with high doses of the antioxidant acetylcysteine appeared to attenuate the progression of IPF (25).”
What the sources say
- Not checked yetcites [25] Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, et al. N Engl J Med. 2005;353:2229–2242. doi: 10.1056/NEJMoa042976. [DOI] [PubMed] [Google Scholar] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This report provides previously undescribed molecular insight into the pathogenesis of IPF and expands the scope of diseases caused by mutations in telomerase.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Telomere length is influenced by many different factors, including age (13, 14) and the number of generations the mutation is transmitted (6, 15).”
What the sources say
- Not checked yetcites [13] Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Nature. 1990;346:866–868. doi: 10.1038/346866a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [14] Harley CB, Futcher AB, Greider CW. Nature. 1990;345:458–460. doi: 10.1038/345458a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [15] Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I. Nat Genet. 2004;36:447–449. doi: 10.1038/ng1346. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study was approved by the University of Texas Southwestern Institutional Review Board. Written informed consent was obtained from all participants.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such a pattern of injury could explain why the pulmonary phenotype is incompletely penetrant and may be influenced not only by the nature of the mutations but also by environmental influences, such as cigarette smoking.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
TERT encodes telomerase reverse transcriptase, which together with TERC is required to maintain telomere integrity.
“TERT encodes telomerase reverse transcriptase, which together with the RNA component of telomerase (TERC), is required to maintain telomere integrity.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The fact that AAV9-TERT treatment of old mice efficiently reactivated telomerase in the lungs offers a therapeutic opportunity for some cases of human pulmonary fibrosis associated with presence of short telomeres owing to telomerase mutations (Armanios et al, 2007; Tsakiri et al, 2007).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Tsakiri et al, 2007
In the citing paper
“The frequency of these mutations is highest in individuals with the progressive disorder IPF, which accounts for 8–15% of familial and 1–3% of sporadic cases54,56,68,69.”
From The telomere syndromes (2012) · cites this paper as [68]
In the citing paper
“By contrast, telomere shortening is accelerated in several human premature ageing syndromes, and patients with dyskeratosis congenita and aplastic anaemia show decreased telomerase activity and shortened telomeres owing to mutations in the TERC and TERT telomerase genes.”
From The common biology of cancer and ageing (2007) · cites this paper as [63]
In the citing paper
“patients who have inherited or acquired genetic defects that limit telomere maintenance seem to be at substantially increased risk of a range of conditions including aplastic anaemia 61 , idiopathic pulmonary fibrosis 62, 63 and the rarer dyskeratosis congenita syndrome”
From The common biology of cancer and ageing (2007) · cites this paper as [63]
Citations
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
(2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.2.ats01 · Cited by 4,196
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Nature Genetics · doi:10.1038/ng786 · Cited by 3,323
Oxidative stress shortens telomeres
von Zglinicki, T. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02110-2 · Cited by 2,524
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion
den Dunnen, J. T., & Antonarakis, S. E. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200001)15:1 · Cited by 1,757
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349
Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
Raghu, G., Weycker, D., Edelsberg, J., Bradford, W. Z., & Oster, G. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200602-163oc · Cited by 1,310
Self-citationIdiopathic Pulmonary Fibrosis: Clinical Relevance of Pathologic Classification
KATZENSTEIN, A.-L. A., & MYERS, J. L. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.9707039 · Cited by 1,261
Cited by
Sorted by citations
Items 201–300 of 892
Cellular senescence in the lung across the age spectrum
Parikh, P., Wicher, S., Khandalavala, K., Pabelick, C. M., Britt, R. D., & Prakash, Y. S. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00424.2018 · Cited by 112
“Patients with IPF also show mutations in telomerase (8, 169, 177) and telomere-lengthening component (8, 56).”
BackgroundGenome-wide association studies in cancer--current and future directions
Chung, C. C., Magalhães, W. C. S., Bosquet, J. G., & Chanock, S. J. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp273 · Cited by 110
Telomere Length in Interstitial Lung Diseases
Snetselaar, R., van Moorsel, C. H. M., Kazemier, K. M., van der Vis, J. J., Zanen, P., van Oosterhout, M. F. M., & Grutters, J. C. (2015) · CHEST Journal · doi:10.1378/chest.14-3078 · Cited by 114
Moore, C. M., Blumhagen, R. Z., Yang, I. V., Walts, A. D., Powers, J., Walker, T., Bishop, M. M., Russell, P. H., Vestal, B. E., Cardwell, J., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201810-1891oc · Cited by 115
“We note, however, that the functional variants in TERT that were previously reported to be relevant for pulmonary fibrosis (3, 23) are in the most significant window we identified in TERT.”
BackgroundMesenchymal stem cells in fibrotic diseases—the two sides of the same coin
Qin, L., Liu, N., Bao, C.-L.-M., Yang, D.-Z., Ma, G.-X., Yi, W.-H., Xiao, G.-Z., & Cao, H.-L. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00952-0 · Cited by 114
“IPF is highly related to some co-morbidities and complications [107].”
BackgroundInfluentialKirwan, M., Vulliamy, T., Marrone, A., Walne, A. J., Beswick, R., Hillmen, P., Kelly, R., Stewart, A., Bowen, D., Schonland, S. O., et al. (2009) · Human Mutation · doi:10.1002/humu.21115 · Cited by 109
“The positions of these mutations are indicated on drawings of (A) the TERT protein, (B) an amino acid sequence alignment of TERT from several species, and (C) the mature TERC molecule (adapted from [Marrone and Dokal, 2006; Tsakiri et al., 2007]).”
BackgroundMethodThe role of telomeres in the ageing of human skin: Telomeres and skin ageing
Buckingham, E. M., & Klingelhutz, A. J. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2010.01242.x · Cited by 109
FBW7 Mediates Senescence and Pulmonary Fibrosis through Telomere Uncapping
Wang, L., Chen, R., Li, G., Wang, Z., Liu, J., Liang, Y., & Liu, J. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.004 · Cited by 112
Smoking and Idiopathic Pulmonary Fibrosis
Oh, C. K., Murray, L. A., & Molfino, N. A. (2012) · Pulmonary Medicine · doi:10.1155/2012/808260 · Cited by 119
“Heterozygous loss-of-function mutations in TERT have been found in up to 15% of kindreds with familial pulmonary fibrosis [108, 109] and in 1% to 3% of sporadic cases [110, 111].”
BackgroundBiomarkers in idiopathic pulmonary fibrosis
Zhang, Y., & Kaminski, N. (2012) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328356d03c · Cited by 113
“Multiple mutations associated with familial and sporadic forms of IPF have been reported including mutations in surfactant [13–15] and telomerase proteins [16,17].”
BackgroundAlthobiani, M. A., Russell, A., Jacob, J., Ranjan, Y., Folarin, A., Hurst, J. R., & Porter, J. C. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1296890 · Cited by 127
de Leon, A. D., Cronkhite, J. T., Yılmaz, C., Brewington, C. C., Wang, R. C., Xing, C., Hsia, C. C. W., & Garcia, C. K. (2011) · CHEST Journal · doi:10.1378/chest.10-2865 · Cited by 114
Self-citationInterstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis
Hunninghake, G. M., Quesada-Arias, L. D., Carmichael, N. E., Manzano, J. M. M., Poli, S., Baumgartner, M. A., DiGianni, L. M., Gampala-Sagar, S., Leone, D. A., Gulati, S., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201908-1571oc · Cited by 110
Duerr, J., Leitz, D. H. W., Szczygieł, M., Dvornikov, D., Fraumann, S. G., Kreutz, C., Zadora, P. K., Agircan, A. S., Konietzke, P., Engelmann, T. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15743-6 · Cited by 113
Fibroblast Senescence in Idiopathic Pulmonary Fibrosis
Lin, Y., & Xu, Z. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.593283 · Cited by 109
The Adventitia: Essential Role in Pulmonary Vascular Remodeling
Stenmark, K. R., Nozik‐Grayck, E., Gerasimovskaya, E. V., Anwar, A., Li, M., Riddle, S. R., & Frid, M. G. (2010) · Comprehensive physiology · doi:10.1002/cphy.c090017 · Cited by 125
“Myofibrob-lasts variant ED-A fibronectin), tenascin-C, osteopontin, and elastin the fibrotic tissues including the remodeled pulmonary adventitia (53, 180, 201, 202).”
Clinical outcomes of lung transplant recipients with telomerase mutations
Tokman, S., Singer, J. P., Devine, M., Westall, G. P., Aubert, J., Tamm, M., Snell, G. I., Lee, J. S., Goldberg, H. J., Kukreja, J., et al. (2015) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2015.05.002 · Cited by 107
Self-citationIdentification of human TERT elements necessary for telomerase recruitment to telomeres
Schmidt, J. C., Dalby, A. B., & Cech, T. R. (2014) · eLife · doi:10.7554/elife.03563 · Cited by 111
Molecular mechanisms of telomere biology disorders
Grill, S., & Nandakumar, J. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.014017 · Cited by 114
“While this mutant shows only a modest decrease in telomerase activity compared with that in the wildtype (58), it is nonetheless defective in telomerase recruitment to telomeres (34).”
BackgroundTelomerase activity is required for bleomycin-induced pulmonary fibrosis in mice
Liu, T., Chung, M. J., Ullenbruch, M. R., Yu, H., Jin, H., Hu, B., Choi, Y. Y., Ishikawa, F., & Phan, S. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32369 · Cited by 108
“Recent human studies of familial IPF, however, suggest an association between certain heterozygous mutations in TERT or TR and IPF in these families (50, 51), with the implication that shortened telomeres caused by deficiency in telomerase activity may play a role in disease pathogenesis.”
BackgroundVulliamy, T., Kirwan, M. J., Beswick, R. W., Hossain, U., Baqai, C., Ratcliffe, A., Marsh, J. C. W., Walne, A. J., & Dokal, I. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024383 · Cited by 105
“Other patients may present with only aplastic anaemia (AA) [29,30], myelodysplastic syndrome (MDS) [31,32], acute myeloid leukaemia (AML) [33] pulmonary fibrosis [34,35] and liver fibrosis [36], and collectively these can be referred to as the ‘telomereopathies’.”
BackgroundNothobranchius furzeri: A Model for Aging Research and More
Platzer, M., & Englert, C. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.06.006 · Cited by 105
Disease progression and clinical outcomes in telomere biology disorders
Niewisch, M. R., Giri, N., McReynolds, L. J., Alsaggaf, R., Bhala, S., Alter, B. P., & Savage, S. A. (2021) · Blood · doi:10.1182/blood.2021013523 · Cited by 105
Lung epithelial stem cells and their niches: Fgf10 takes center stage
Volckaert, T., & Langhe, S. D. (2014) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-7-8 · Cited by 106
“Widespread damage to the epithelium and/or exhaustion of the epithelial stem cell pool, such as in IPF patients with certain telomerase mutations [142-149], ultimately leads to epithelial loss.”
BackgroundMUC5B and Idiopathic Pulmonary Fibrosis
Yang, I. V., Fingerlin, T. E., Evans, C. M., Schwarz, M. I., & Schwartz, D. A. (2015) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201503-110aw · Cited by 103
TERT gene: its function and dysregulation in cancer
Colebatch, A. J., Dobrovic, A., & Cooper, W. A. (2019) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2018-205653 · Cited by 104
“6”
The telomere/telomerase system in autoimmune and systemic immune-mediated diseases
Georgin-Lavialle, S., Aouba, A., Mouthon, L., Londono-Vallejo, J. A., Lepelletier, Y., Gabet, A.-S., & Hermine, O. (2010) · Autoimmunity Reviews · doi:10.1016/j.autrev.2010.04.004 · Cited by 97
“In summary, the telomere length of peripheral blood mononuclear cells (PBMC) is shorter, when compared to age-matched healthy controls, in patients with systemic lupus erythematosus [7,8,11,12,14], rheumatoid arthritis [15–17,34], Wegener's granulomatosis [21], sarcoidosis [23], systemic sclerosis [24], idiopathic pul…”
BackgroundResultInfluentialFingerlin, T. E., Zhang, W. E., Yang, I. V., Ainsworth, H. C., Russell, P. H., Blumhagen, R. Z., Schwarz, M. I., Brown, K. M., Steele, M. P., Loyd, J. E., et al. (2016) · BMC Genetics · doi:10.1186/s12863-016-0377-2 · Cited by 105
“There is evidence for the importance of environmental factors [3–13] and both rare [14–21] and common genetic variation [22–29] in risk of fIIP.”
BackgroundSelf-citationFernandez, B. A., Fox, G. A., Bhatia, R., Sala, E., Noble, B., Denic, N., Fernandez, D., Duguid, N., Dohey, A., Kamel, F., et al. (2012) · Respiratory Research · doi:10.1186/1465-9921-13-64 · Cited by 103
“This variant has been previously published and proven to be pathogenic [15].”
BackgroundTwo Pathways Recruit Telomerase to Saccharomyces cerevisiae Telomeres
Chan, A., Boulé, J.-B., & Zakian, V. A. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000236 · Cited by 100
“Reducing this already low level by mutation in one of several telomerase components [36–39] or by altering a telomere structural protein [40] can cause fatal diseases, such as dyskeratosis congenita or idiopathic pulmonary fibrosis [41,42].”
BackgroundAssociation between telomere length and survival in patients with idiopathic pulmonary fibrosis
Dai, J., Cai, H., Li, H., Zhuang, Y., Min, H., Wen, Y., Yang, J., Gao, Q., Shi, Y. P., & Yi, L. (2015) · Respirology · doi:10.1111/resp.12566 · Cited by 96
Telomeres, stem cells, and hematology
Lansdorp, P. M. (2008) · Blood · doi:10.1182/blood-2007-09-084913 · Cited by 97
Novel insights from a multiomics dissection of the Hayflick limit
Chan, M., Yuan, H., Soifer, I., Maile, T. M., Wang, R. Y., Ireland, A., O'Brien, J. J., Goudeau, J., Chan, L. J., Vijay, T., et al. (2022) · eLife · doi:10.7554/elife.70283 · Cited by 99
“( Tsakiri et al., 2007 ; Armanios et al., 2007 ; Cronkhite et al., 2008 ; Alder et al., 2008 ; Stuart et al., 2015 ; Raghu et al., 2006 ; Duckworth et al., 2021 ; Stuart et al., 2014 ; Dai et al., 2015 ).”
Lung Cancer and Interstitial Lung Diseases: A Systematic Review
Archontogeorgis, K., Steiropoulos, P., Τzouvelekis, Α., Nena, E., & Bouros, D. E. (2012) · Pulmonary Medicine · doi:10.1155/2012/315918 · Cited by 95
“Mutations in TERT gene which encodes the catalytic component of telomerase and one heterozygous mutation in TERC which is the essential RNA component of telomerase were associated with increased susceptibility to developing IPF [19].”
BackgroundModern Concepts on the Role of Inflammation in Pulmonary Fibrosis
Homer, R., Elias, J. A., Lee, C. G., & Herzog, E. L. (2011) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2010-0296-ra.1 · Cited by 93
The Role of TGF-β Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
Saito, A., Horie, M., Micke, P., & Nagase, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113611 · Cited by 94
Genetic Evaluation and Testing of Patients and Families with Idiopathic Pulmonary Fibrosis
Kropski, J. A., Young, L. R., Cogan, J. D., Mitchell, D. B., LANCASTER, L. H., Worrell, J. A., Markin, C. R., Liu, N., Mason, W. R., Fingerlin, T. E., et al. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201609-1820pp · Cited by 96
Dinardo, C. D., Bannon, S. A., Routbort, M. J., Franklin, A. R. K., Mork, M. E., Armanios, M. Y., Mace, E. M., Orange, J. S., Jeff‐Eke, M., Churpek, J. E., et al. (2016) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2016.04.001 · Cited by 90
“One 53-year-old male with a personal history of MDS, pulmonary fibrosis, short stature, premature grey hair, whose father and brother also have idiopathic pulmonary fibrosis, had an age-adjusted TL <1% in lymphocytes and granulocytes consistent with a telomeropathy, and a pathogenic heterozygous TERT R865H variant on…”
BackgroundInfluence of age on wound healing and fibrosis
Kapetanaki, M. G., Mora, A. L., & Rojas, M. M. (2012) · The Journal of Pathology · doi:10.1002/path.4122 · Cited by 92
Targeting NOX enzymes in pulmonary fibrosis
Hecker, L., Cheng, J., & Thannickal, V. J. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1012-7 · Cited by 90
“More recent concepts have focused on the possibility that IPF may represent a degenerative disease of aging; studies of familial and sporadic cases of IPF have been associated with telomere shortening [3, 13, 55], supporting the concept that IPF may represent an age-related degenerative disease process [53].”
BackgroundChen, R., Zhang, K., Chen, H., Zhao, X., Wang, J., Li, L., Cong, Y., Ju, Z., Xu, D., Williams, B. R. G., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.681619 · Cited by 89
Chromatin regulation and non-coding RNAs at mammalian telomeres
Schoeftner, S., & Blasco, M. A. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.09.015 · Cited by 96
Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations
Maryoung, L. A., Yue, Y., Young, A. M., Newton, C. A., Barba, C., van Oers, N. S. C., Wang, R. C., & Garcia, C. K. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91161 · Cited by 88
“Three germline TERT missense alleles, Lys570Asn, Arg631Gln, and Arg865His, are associated with a severe reduction of telomerase activity and processivity (8, 12, 13).”
BackgroundSelf-citationLucid, C., Savani, B. N., Engelhardt, B. G., Shah, P. D., Clifton, C., Greenhut, S. L., Vaughan, L. A., Kassim, A. A., Schuening, F., & Jagasia, M. (2010) · Bone Marrow Transplantation · doi:10.1038/bmt.2010.152 · Cited by 87
S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose
Behr, J., Günther, A., Ammenwerth, W., Bittmann, I., Bonnet, R. B., Buhl, R., Eickelberg, O., Ewert, R., Gläser, S., Gottlieb, J., et al. (2013) · Pneumologie · doi:10.1055/s-0032-1326009 · Cited by 90
Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis
Takeda, Y., Tsujino, K., Kijima, T., & Kumanogoh, A. (2014) · Patient Preference and Adherence · doi:10.2147/ppa.s37233 · Cited by 87
Telomeres in Interstitial Lung Disease: The Short and the Long of It
Courtwright, A., & El‐Chemaly, S. (2018) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201808-508cme · Cited by 86
DNA variations in human and medical genetics: 25 years of my experience
Nakamura, Y. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2008.6 · Cited by 86
Tobacco Smoke–Induced Lung Fibrosis and Emphysema
Morse, D., & Rosas, I. O. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170411 · Cited by 90
Telomerase and Telomere Length in Pulmonary Fibrosis
Liu, T., Ullenbruch, M. R., Choi, Y. Y., Yu, H., Ding, L., Xaubet, A., Pereda, J., Feghali‐Bostwick, C. A., Bitterman, P. B., Henke, C. A., et al. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0514oc · Cited by 83
Genetics and Early Detection in Idiopathic Pulmonary Fibrosis
Putman, R. K., Rosas, I. O., & Hunninghake, G. M. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201312-2219pp · Cited by 84
Lung Transplant Outcomes in Patients With Pulmonary Fibrosis With Telomere-Related Gene Variants
Swaminathan, A. C., Neely, M. L., Frankel, C. W., Kelly, F. L., Petrovski, S., Durheim, M. T., Bush, E., Snyder, L. D., Goldstein, D. B., Todd, J. L., et al. (2019) · CHEST Journal · doi:10.1016/j.chest.2019.03.030 · Cited by 83
Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease
Zhang, D., Adegunsoye, A., Oldham, J. M., Kozlitina, J., Garcia, N. M., Poonawalla, M., Strykowski, R. K., Linderholm, A., Ley, B., Ma, S., et al. (2023) · European Respiratory Journal · doi:10.1183/13993003.00441-2023 · Cited by 86
“Telomere dysfunction has been inexorably linked with ILD development and disease trajectory [3 – 12].”
Self-citationHomeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair
Kumar, V., Fleming, T. H., Terjung, S., Gorzelanny, C., Gebhardt, C., Agrawal, R., Mall, M. A., Ranzinger, J., Zeier, M. G., Madhusudhan, T., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx705 · Cited by 82
“Similarly, the absence of a functional telomere maintaining enzyme, telomerase (33,101,102), or cellular stress that generates dysfunctional telomeres (102), lead to a persistent DNA damage signaling cascade (103,104).”
BackgroundSaux, C. J. L., Davy, P. M. C., Brampton, C. N., Ahuja, S. S., Fauce, S. R., Shivshankar, P., Nguyen, H., Ramaseshan, M., Tressler, R., Pirot, Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058423 · Cited by 82
“Together, these data also suggest that the design of truly effective therapies to treat IPF involving telomerase activation warrants careful attention to the specific lung cell type targeted by the drug.”
BackgroundInfluentialIdiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants
Peljto, A. L., Blumhagen, R. Z., Walts, A. D., Cardwell, J., Powers, J., Corte, T. J., Dickinson, J. L., Glaspole, I., Moodley, Y. P., Vašáková, M., et al. (2023) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202207-1331oc · Cited by 85
Genetic Basis of Children's Interstitial Lung Disease
Nogee, L. M. (2010) · Pediatric Allergy Immunology and Pulmonology · doi:10.1089/ped.2009.0024 · Cited by 80
Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis.
Chilosi, M., Doglioni, C., Murer, B., & Poletti, V. E. (2010) · Sarcoidosis vasculitis and diffuse lung diseases · Cited by 78
Genetic determinants of pulmonary fibrosis: evolving concepts
Spagnolo, P., Grünewald, J., & du Bois, R. M. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70047-5 · Cited by 85
Management of suspected monogenic lung fibrosis in a specialised centre
Borie, R., Kannengiesser, C., de Fontbrune, F. S., Gouya, L., Nathan, N., & Crestani, B. (2017) · European Respiratory Review · doi:10.1183/16000617.0122-2016 · Cited by 84
Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes
Wei, R., Li, C., Zhang, M., Jones‐Hall, Y., Myers, J. L., Noth, I., & Liu, W. (2013) · Translational research · doi:10.1016/j.trsl.2013.12.006 · Cited by 83
Bessler, M., Wilson, D. B., & Mason, P. J. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.05.019 · Cited by 83
Varma, S., Cao, Y., Tagne, J.-B., Lakshminarayanan, M., Li, J., Friedman, T. B., Morell, R. J., Warburton, D., Kotton, D. N., & Ramirez, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.408401 · Cited by 79
Dyskeratosis Congenita: A historical perspective
Walne, A. J., & Dokal, I. S. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.10.006 · Cited by 81
Idiopathic Pulmonary Fibrosis—an Epidemiological and Pathological Review
Borchers, A. T., Chang, C. C., Keen, C. L., & Gershwin, M. E. (2010) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8211-5 · Cited by 80
“Telomerase mutations were identified in only 1–3% of patients with sporadic IPF [37–39].”
BackgroundRobart, A. R., & Collins, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088575 · Cited by 80
Pulmonary fibrosis in the era of stratified medicine
Mathai, S. K., Newton, C. A., Schwartz, D. A., & Garcia, C. K. (2016) · Thorax · doi:10.1136/thoraxjnl-2016-209172 · Cited by 77
Self-citationEmerging delivery approaches for targeted pulmonary fibrosis treatment
Diwan, R., Bhatt, H., Beaven, E., & Nurunnabi, M. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115147 · Cited by 81
Cellular Senescence in Lung Fibrosis
Hernández‐González, F., Faner, R., Rojas, M. M., Agustí, A. G. N., Serrano, M., & Sellarés, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137012 · Cited by 79
Mimeault, M., & Batra, S. K. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2008.12.001 · Cited by 77
The role of telomere biology in bone marrow failure and other disorders
Savage, S. A., & Alter, B. P. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.002 · Cited by 75
“This group will include patents with telomere biology abnormalities as well as BMF that fails to respond to immunosuppression, IPF, and possibly other yet-to-be-identified disorders (Table 1).”
BackgroundInfluentialNeglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis
Cordier, J.-F., & Cottin, V. (2013) · European Respiratory Journal · doi:10.1183/09031936.00027913 · Cited by 76
Human Telomeres and Telomere Biology Disorders
Savage, S. A. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-397898-1.00002-5 · Cited by 78
Genetics of idiopathic pulmonary fibrosis: from mechanistic pathways to personalised medicine
Spagnolo, P., & Cottin, V. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-103973 · Cited by 81
Ethnic and racial differences in the presence of idiopathic pulmonary fibrosis at death
Swigris, J. J., Olson, A. L., Huie, T. J., Pérez, E. R. F., Solomon, J. J., Sprunger, D. B., & Brown, K. K. (2012) · Respiratory Medicine · doi:10.1016/j.rmed.2012.01.002 · Cited by 75
Determinants of initiation and progression of idiopathic pulmonary fibrosis
Kottmann, R. M., Hogan, C. M., Phipps, R. P., & Sime, P. J. (2009) · Respirology · doi:10.1111/j.1440-1843.2009.01624.x · Cited by 74
Calado, R. T. (2009) · Hematology · doi:10.1182/asheducation-2009.1.338 · Cited by 74
Many disease-associated variants of hTERT retain high telomerase enzymatic activity
Zaug, A. J., Crary, S. M., Fioravanti, M. J., Campbell, K. P., & Cech, T. R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt653 · Cited by 73
“In most cases, they observed activity that was intermediate between that of the individual alleles, indicating that the disease phenotype is due to haploinsufficiency rather than dominant negative inhibition (10,18,19,33,37,38,47,48).”
BackgroundFactors impacting human telomere homeostasis and age-related disease
Gilley, D. P., Herbert, B., Huda, N., Tanaka, H., & Reed, T. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.10.010 · Cited by 74
Defective telomere elongation and hematopoiesis from telomerase-mutant aplastic anemia iPSCs
Winkler, T., Hong, S. G., Decker, J. E., Morgan, M. J., Wu, C., Hughes, W. M., Yang, Y., Wangsa, D., Padilla‐Nash, H. M., Ried, T., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67146 · Cited by 73
“Telomerase mutations are genetic risk factors for apparently acquired aplastic anemia (6), idiopathic pulmonary fibrosis (7, 8), liver disorders (9–11), and acute myeloid leukemia (12, 13).”
Is Progression of Pulmonary Fibrosis due to Ventilation-induced Lung Injury?
Albert, R. K., Smith, B. J., Perlman, C. E., & Schwartz, D. A. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201903-0497pp · Cited by 73
MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis
Mathai, S. K., Humphries, S. M., Kropski, J. A., Blackwell, T. S., Powers, J., Walts, A. D., Markin, C. R., Woodward, J., Chung, J. H., Brown, K. K., et al. (2019) · Thorax · doi:10.1136/thoraxjnl-2018-212430 · Cited by 72
“4 5 8 Numerous rare variants in TERT (and other telomerase-pathway genes) have been thought to be critical in familial diseases 6 9–11 ; more recently, a common variant in TERT 5 has been associated with sporadic and familial disease.”
Adegunsoye, A., Kropski, J. A., Behr, J., Blackwell, T. S., Corte, T. J., Cottin, V., Glanville, A. R., Glassberg, M. K., Griese, M., Hunninghake, G. M., et al. (2024) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202401-0238so · Cited by 82
Understanding COPD-overlap syndromes
Poh, T. Y., Aogáin, M. M., Chan, A., Yii, A. C. A., Yong, V. F. L., Tiew, P. Y., Koh, M. S., & Chotirmall, S. H. (2017) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2017.1305895 · Cited by 73
Endothelin in Pulmonary Fibrosis
Fonseca, C., Abraham, D., & Renzoni, E. A. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2009-0388tr · Cited by 72
Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night
Schiza, S. E., Mermigkis, C. M., Margaritopoulos, G. A., Daniil, Z. D., Harari, S. A., Poletti, V. E., Renzoni, E. A., Torre, O., Visca, D., Bouloukaki, I., et al. (2015) · European Respiratory Review · doi:10.1183/16000617.00009114 · Cited by 74
Update on the diagnosis and classification of ILD
Ryerson, C. J., & Collard, H. R. (2013) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328363f48d · Cited by 70
van der Vis, J. J., Snetselaar, R., Kazemier, K. M., ten Klooster, L., Grutters, J. C., & van Moorsel, C. H. M. (2015) · Respirology · doi:10.1111/resp.12728 · Cited by 75
Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs
Hadjicharalambous, M. R., & Lindsay, M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020524 · Cited by 70
“TERT and TERC encode telom rase genes which restore t lomere length and muta ions lead to increased telomere shortening.”
BackgroundDyskeratosis congenita: The first NIH clinical research workshop
Savage, S. A., Dokal, I. S., Armanios, M. Y., Aubert, G., Cowen, E. W., Domingo, D. L., Giri, N., Greene, M. H., Orchard, P. J., Tolar, J., et al. (2009) · Pediatric Blood & Cancer · doi:10.1002/pbc.22061 · Cited by 69
“TERT and TERC mutations have been found in patients with pulmonary fibrosis and patients with apparently acquired aplastic anemia; these patients did not have the classic triad of DC [23,18,24,25].”
BackgroundEpidemiology and comorbidities in idiopathic pulmonary fibrosis: a nationwide cohort study
Lee, J. H., Park, H. J., Kim, S., Kim, Y., & Kim, H. C. (2023) · BMC Pulmonary Medicine · doi:10.1186/s12890-023-02340-8 · Cited by 72
“Because the ageing process influences the pathogenesis of IPF, comorbidities must be carefully monitored and managed in patients with IPF, especially in older patients [35, 36].”
BackgroundGiri, N., Lee, R. L., Faro, A., Huddleston, C. B., White, F. V., Alter, B. P., & Savage, S. A. (2011) · BMC Blood Disorders · doi:10.1186/1471-2326-11-3 · Cited by 70
Kozlitina, J., & Garcia, C. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051046 · Cited by 69
“While DC is the most severe clinical manifestation of telomerase dysfunction, rare germline mutations in the telomerase genes (TERT and TERC) have also been found in patients with isolated aplastic anemia [8], myelodysplastic syndrome [9], acute myeloid leukemia [10], pulmonary fibrosis [11,12] and liver cirrhosis [13…”
BackgroundSelf-citationCurrent Insights to Regulation and Role of Telomerase in Human Diseases
Ozturk, M. B., Li, Y., & Tergaonkar, V. (2017) · Antioxidants · doi:10.3390/antiox6010017 · Cited by 68
“Apart from cancer, impairment in TERT may cause telomere shortening, resulting in age-related diseases such as idiopathic pulmonary fibrosis (IPF), dyskeratosis congenita and aplastic anemia [20].”
BackgroundPulmonary phenotypes associated with genetic variation in telomere-related genes
Hoffman, T. W., van Moorsel, C. H. M., Borie, R., & Crestani, B. (2018) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000475 · Cited by 68
Wu, A. C., Kiley, J. P., Noel, P. J., Amur, S., Burchard, E. G., Clancy, J. P., Galanter, J., Inada, M., Jones, T. K., Kropski, J. A., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201810-1895st · Cited by 69
The genetics of interstitial lung diseases
Borie, R., Guen, P. L., Ghanem, M., Taillé, C., Dupin, C., Dieudé, P., Kannengiesser, C., & Crestani, B. (2019) · European Respiratory Review · doi:10.1183/16000617.0053-2019 · Cited by 75
Mattijssen, S., Welting, T. J. M., & Pruijn, G. J. M. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.9 · Cited by 66
Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita
Parry, E. M., Alder, J. K., Lee, S. S., Phillips, J. A., Loyd, J. E., Duggal, P., & Armanios, M. Y. (2011) · Journal of Medical Genetics · doi:10.1136/jmg.2010.085100 · Cited by 69
Idiopathic Pulmonary Fibrosis and the Elderly: Diagnosis and Management Considerations
Jo, H. E., Randhawa, S., Corte, T. J., & Moodley, Y. P. (2016) · Drugs & Aging · doi:10.1007/s40266-016-0366-1 · Cited by 68
Metadata
- Authors
- Tsakiri, K. D., Cronkhite, J. T., Kuan, P. J., Xing, C., Raghu, G., Weissler, J. C., Rosenblatt, R. L., Shay, J. W., & Garcia, C. K.
- Affiliations
- *McDermott Center for Human Growth and Development,
- University of Washington Medical Center (US)
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,
- The University of Texas Southwestern Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-05
- Volume
- 104
- Issue
- 18
- Pages
- 7552-7557
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1855917
- OpenAlex
- W2115176808
- Cited by
- 894
- References
- 35
- Citations by year
- 2026: 24 · 2025: 35 · 2024: 30 · 2023: 35 · 2022: 49 · 2021: 62 · 2020: 54 · 2019: 43 · 2018: 45 · 2017: 41 · 2016: 40 · 2015: 61 · 2014: 50 · 2013: 50 · 2012: 53
- FWCI
- 47.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P50CA75907, P50CA070907)
- National Center for Research Resources (K23RR020632)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, telomerase reverse transcriptase, TERC, telomerase RNA, telomere shortening, genetic linkage, familial pulmonary fibrosis, missense mutations, frameshift mutation, interstitial lung disease, genetic susceptibility, chromosome 5
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Pulmonary Fibrosis, Sequence Alignment, Telomere, Age of Onset, Telomerase
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